Cellular responses to micro- and nanoplastics exposure: mechanisms and pathophysiological implications

Abstract Microplastics (MPs) and nanoplastics (NPs) are increasingly detected in environmental matrices and human biological samples, raising concern about their potential effects on cellular function and human health. This structured narrative review critically evaluates evidence from in vitro, in vivo, ex vivo, and human studies, with emphasis on the mechanisms governing particle–cell interactions and the methodological limitations that affect interpretation. Cellular contact, uptake, intracellular trafficking, and delivered dose are influenced by particle size, shape, polymer composition, surface chemistry, environmental aging, aggregation state, and biocorona formation. Experimental studies have recurrently reported lysosomal and mitochondrial dysfunction, oxidative stress, inflammatory signaling, impaired autophagic clearance, genomic instability, metabolic disruption, and barrier dysfunction following MNP exposure. These responses are highly interconnected and may form self-reinforcing stress networks rather than independent pathways. However, their magnitude and biological relevance vary substantially according to particle characteristics, exposure concentration and duration, and experimental model. Human studies demonstrate the presence of plastic-associated material in blood and selected tissues, supporting systemic exposure and possible translocation, but do not by themselves establish intracellular toxicity or causal relationships with specific diseases. Translation of experimental findings is further limited by inconsistent particle characterization, non-equivalent dose metrics, contamination risk, and the frequent use of short-term exposures at concentrations exceeding reported human burdens. Greater mechanistic and translational confidence will require standardized exposure and dosimetry frameworks, chronic low-dose studies, environmentally relevant particles, human-relevant multicellular models, organoids and organ-on-chip platforms, multi-omics integration, and validated imaging and biosensing approaches. Overall, current evidence supports the biological plausibility of MNP-induced cellular injury, but remains insufficient to establish direct causation between MNP exposure and specific human diseases. Graphical abstract